Flux-based classification of reactions reveals a functional bow-tie organization of complex metabolic networks

Shalini Singh 12, Areejit Samal 134, Varun Giri 1, Sandeep Krishna 5, Nandula Raghuram 6, Sanjay Jain 178

Physical Review E 87 (2013) 052708

Unraveling the structure of complex biological networks and relating it to their functional role is an important task in systems biology. Here we attempt to characterize the functional organization of the large-scale metabolic networks of three microorganisms. We apply flux balance analysis to study the optimal growth states of these organisms in different environments. By investigating the differential usage of reactions across flux patterns for different environments, we observe a striking bimodal distribution in the activity of reactions. Motivated by this, we propose a simple algorithm to decompose the metabolic network into three sub-networks. It turns out that our reaction classifier which is blind to the biochemical role of pathways leads to three functionally relevant sub-networks that correspond to input, output and intermediate parts of the metabolic network with distinct structural characteristics. Our decomposition method unveils a functional bow-tie organization of metabolic networks that is different from the bow-tie structure determined by graph-theoretic methods that do not incorporate functionality.

  • 1 : Department of Physics and Astrophysics
    University of Delhi
  • 2 : Department of Genetics
    University of Delhi
  • 3 : Max Planck Institute for Mathematics in the Sciences (MPI-MIS)
    Max-Planck-Institut
  • 4 : Laboratoire de Physique Théorique et Modèles Statistiques (LPTMS)
    CNRS : UMR8626 – Université Paris XI - Paris Sud
  • 5 : National Centre for Biological Sciences
    UAS-GKVK Campus
  • 6 : School of Biotechnology
    GGS Indraprastha University
  • 7 : Jawaharlal Nehru Centre for Advanced Scientific Research
    Jawaharlal Nehru Centre for Advanced Scientific Research
  • 8 : Santa Fe Institute
    Santa Fe Institute